The biocompatibility of implantable medical devices can be improved by a variety of known methods, most notably by surface modification, such as the addition of a coating material. For example, it is known that ophthalmic lenses may be coated with a coating material. U.S. Pat. No. 4,170,043 discloses intraocular lenses (IOLs) coated with a film that dissolves slowly in water. This helps prevent endothelial damage upon implantation of the IOL. The coating dissolves within about 24 hours after implantation.
U.S. Pat. No. 4,731,080 discloses a coated IOL, wherein the lens is coated with a non-smudging, biologically compatible hydrophobic cross-linked vinyl-containing silicone polymer coating material.
U.S. Pat. No. 5,080,924 discloses a method of modifying the surface of a substrate using radio frequency plasma-induced grafting. In this procedure, which may be used on an IOL, a first biocompatible material, preferably having pendant carboxylic acid or amine groups, is covalently grafted to the surface of a substrate polymer core by radio frequency plasma induction. A second biocompatible material then may be grafted to the first biocompatible material using a cross-linking agent.
A series of patents disclose contact lenses which are coated by various materials including polyethylene oxide (PEO). Such patents include U.S. Pat. Nos. 4,280,970; 4,871,785; 4,740,533; 5,070,166; and 5,096,626. U.S. Pat. No. 4,280,970 discloses coating a contact lens by grafting PEO thereto.
U.S. Pat. No. 5,308,641 discloses an improved spacer material for improving the biocompatibility of a biomaterial and a method for making it in which a polyalkylimine is covalently attached to an aminated substrate and combined with a cross-linking agent which is at least difunctional in aldehyde groups. The polyalkylimine can be, for example, polyethyleneimine and the cross-linking agent can be, for example, glutaraldehyde. Preferably, the cross-linking agent is applied in dilute solution and at a pH suitable to accomplish light cross-linking of the polyalkylimine and also provide aldehyde linkages at the interface between the biomolecule and the spacer.
U.S. Pat. No. 5,290,548, assigned to the University of Florida, discloses PEO coated instruments, devices, implants, contact lenses and the like. The PEO coating is created using gamma radiation to polymerize vinyl-functionalized PEO directly onto the surface of the instrument, device, etc.
U.S. Pat. No. 4,973,493 discloses a method for modifying a surface to improve its biocompatibility. The method employs molecules of a biocompatible agent and a chemical linking moiety possessing two different photochemically reactive groups, one group which reacts with the surface and one which reacts with the biocompatible agent. The method comprises applying stimulus to sequentially activate the groups to covalently bind the linking moiety to the molecules of the biocompatible agent and to photochemically covalently bind the linking moiety to the surface of the device. In one embodiment, the molecules of the biocompatible material are joined together to form a film that is attached to the surface of the device by the linking moiety. In this embodiment, the biocompatible agent desirably may be hyaluronic acid or albumin. A biocompatible device having such a film attached may be an artificial hip joint coated with a film of hyaluronic acid. No mention is made of sterilization of the devices.
Commonly assigned, co-pending U.S. patent application Ser. No. 08/166,033, discloses intraocular lenses coated with PEO applied through amine covalent bonding. However, when these lenses are sterilized with ethylene-oxide (EtO) sterilization and then aerated to remove residual EtO, some of the protein and cell repulsion ability of the PEO coating is lost. U.S. Ser. No. 08/166,033 discloses an aqueous extraction step in place of the conventional aeration step to minimize the coating's loss of protein and cell repulsion ability.
What is needed are additional coatings and processes for improving the biocompatibility of implantable medical devices which must survive EtO sterilization procedures.